Particulate matter neurotoxicity in culture is size-dependent

Exposure to particulate matter (PM) air pollution produces inflammatory damage to the cardiopulmonary system. This toxicity appears to be inversely related to the size of the PM particles, with the ultrafine particle being more inflammatory than larger sizes. Exposure to PM has more recently been associated with neurotoxicity. This study examines if the size-dependent toxicity reported in cardiopulmonary systems also occurs in neural targets. For this study, PM ambient air was collected over a 2 week period from Sterling Forest State Park (Tuxedo, New York) and its particulates sized as Accumulation Mode, Fine (AMF) (>0.18-1μm) or Ultrafine (UF) (12.5μg/ml) but was only significant at the highest concentration of AMF (50μg/ml). To examine if PM size-dependent neurotoxicity was retained in the presence of other cell types, dissociated brain cultures of embryonic rat striatum were exposed to AMF (80μg/ml) or UF (8.0μg/ml). After 24h exposure, a significant increase of reactive nitrogen species (nitrite) and morphology suggestive of apoptosis occurred in both treatment groups. However, morphometric analysis of neuron specific enolase staining indicated that only the UF exposure produced significant neuronal loss, relative to controls. Together, these data suggest that the inverse relationship between size and toxicity reported in cardiopulmonary systems occurs in cultures of isolated dopaminergic neurons and in primary cultures of the rat striatum

Translocation and potential neurological effects of fine and ultrafine particles a critical update

ABSTRACT: Particulate air pollution has been associated with respiratory and cardiovascular disease. Evidence for cardiovascular and neurodegenerative effects of ambient particles was reviewed as part of a workshop. The purpose of this critical update is to summarize the evidence presented for the mechanisms involved in the translocation of particles from the lung to other organs and to highlight the potential of particles to cause neurodegenerative effects.Fine and ultrafine particles, after deposition on the surfactant film at the air-liquid interface, are displaced by surface forces exerted on them by surfactant film and may then interact with primary target cells upon this displacement. Ultrafine and fine particles can then penetrate through the different tissue compartments of the lungs and eventually reach the capillaries and circulating cells or constituents, e.g. erythrocytes. These particles are then translocated by the circulation to other organs including the liver, the spleen, the kidneys, the heart and the brain, where they may be deposited. It remains to be shown by which mechanisms ultrafine particles penetrate through pulmonary tissue and enter capillaries. In addition to translocation of ultrafine particles through the tissue, fine and coarse particles may be phagocytized by macrophages and dendritic cells which may carry the particles to lymph nodes in the lung or to those closely associated with the lungs. There is the potential for neurodegenerative consequence of particle entry to the brain. Histological evidence of neurodegeneration has been reported in both canine and human brains exposed to high ambient PM levels, suggesting the potential for neurotoxic consequences of PM-CNS entry. PM mediated damage may be caused by the oxidative stress pathway. Thus, oxidative stress due to nutrition, age, genetics among others may increase the susceptibility for neurodegenerative diseases. The relationship between PM exposure and CNS degeneration can also be detected under controlled experimental conditions. Transgenic mice (Apo E -/-), known to have high base line levels of oxidative stress, were exposed by inhalation to well characterized, concentrated ambient air pollution. Morphometric analysis of the CNS indicated unequivocally that the brain is a critical target for PM exposure and implicated oxidative stress as a predisposing factor that links PM exposure and susceptibility to neurodegeneration.Together, these data present evidence for potential translocation of ambient particles on organs distant from the lung and the neurodegenerative consequences of exposure to air pollutants

Nanosize Titanium Dioxide Stimulates Reactive Oxygen Species in Brain Microglia and Damages Neurons in Vitro

BackgroundTitanium dioxide is a widely used nanomaterial whose photo-reactivity suggests that it could damage biological targets (e.g., brain) through oxidative stress (OS).ObjectivesBrain cultures of immortalized mouse microglia (BV2), rat dopaminergic (DA) neurons (N27), and primary cultures of embryonic rat striatum, were exposed to Degussa P25, a commercially available TiO2 nanomaterial. Physical properties of P25 were measured under conditions that paralleled biological measures.FindingsP25 rapidly aggregated in physiological buffer (800–1,900 nm; 25°C) and exposure media (~ 330 nm; 37°C), and maintained a negative zeta potential in both buffer (–12.2 ± 1.6 mV) and media (–9.1 ± 1.2 mV). BV2 microglia exposed to P25 (2.5–120 ppm) responded with an immediate and prolonged release of reactive oxygen species (ROS). Hoechst nuclear stain was reduced after 24-hr (≥100 ppm) and 48-hr (≥2.5 ppm) exposure. Microarray analysis on P25-exposed BV2 microglia indicated up-regulation of inflammatory, apoptotic, and cell cycling pathways and down-regulation of energy metabolism. P25 (2.5–120 ppm) stimulated increases of intracellular ATP and caspase 3/7 activity in isolated N27 neurons (24–48 hr) but did not produce cytotoxicity after 72-hr exposure. Primary cultures of rat striatum exposed to P25 (5 ppm) showed a reduction of immunohistochemically stained neurons and microscopic evidence of neuronal apoptosis after 6-hr exposure. These findings indicate that P25 stimulates ROS in BV2 microglia and is nontoxic to isolated N27 neurons. However, P25 rapidly damages neurons at low concentrations in complex brain cultures, plausibly though microglial generated ROS

Murine susceptibility to organophosphorus-induced delayed neuropathy (OPIDN)

This study reports that CD-1 strain mice are neuropathologically and biochemically responsive to acute doses of tri-ortho-cresyl phosphate (TOCP). Young (25–30 g) male and female animals were exposed (po) to a single dose of TOCP (580–3480 mg/kg) and sampled for neurotoxic esterase (NTE) activity at 24 and 44 hr postexposure and for neuropathic damage 14 days later. Biochemically, high intragroup variability existed at the lower doses, and at higher levels of TOCP exposure (i.e., ≥ 1160 mg/kg), mean brain NTE inhibition never exceeded 68%. Hen and mouse brain NTE activity, assayed in vitro for sensitivity to inhibition by tolyl saligenin phosphate (TSP), the active neurotoxic metabolite of TOCP, showed similar IC50 values. Histologically, highly variable spinal cord damage was recorded throughout treatment groups and mean damage scores followed a dose-response pattern with no apparent correlation to threshold (i.e., ≥ 65%) inhibition of brain NTE activity. Topographically, axonal degeneration in the mouse spinal cord predominated in the lateral and ventral columns of the upper cervical cord. Unlike the rat, which displays degeneration in the upper cervical cord's dorsal columns (i.e., gracilis fasciculus) in response to TOCP intoxication, treated mice showed minimal damage to this tract. To examine this discrepancy further, ultrastructural morphometric analysis of axon diameters in the cervical cord was performed in control mice and rats. These results indicated that in both species, the largest diameter (≥ 4 μm) axons are housed in the ventral columns of the cervical spinal cord, suggesting that axon length and diameter may not be the only criteria underlying fiber tract vulnerability in OPIDN

Linking the Physicochemical Properties of Calcined Titania Nanoparticles with Their Biocidal Activity

Titanium dioxide nanoparticles (nTiO2) show biocidal activity when exposed to UV illumination. Modification of their physical properties can expand their photoresponse region toward visible light. In this study, such modification was made through a sol-gel synthesis followed by calcination at a range of temperatures (250–900 °C), generating a series of nTiO2 particles with different crystal phases, sizes, porosities, zeta potentials, and BET surface areas. The unique properties of nTiO2 were linked to their toxicity to the marine bacterium, Vibrio fischeri. A modified “Flash” high-through put assay was used to test the viability of these marine organisms after short term (15–60 min) exposure under visible light only to the individual groups of nTiO2 (500–2000 μg/mL). Linear regression analysis indicated that across all concentrations and time points, high biocidal activity correlated with the amorphous and anatase crystal phases, high BET surface area, high pore volume and small crystal size. The linkage between physicochemistry and nanotoxicity would be helpful for future design of more efficient and sustainable nTiO2

The Physicochemistry of Capped Nanosilver Predicts Its Biological Activity in Rat Brain Endothelial Cells (RBEC4)

The “capping” or coating of nanosilver (nanoAg) extends its potency by limiting its oxidation and aggregation and stabilizing its size and shape. The ability of such coated nanoAg to alter the permeability and activate oxidative stress pathways in rat brain endothelial cells (RBEC4) was examined in the present study. The aggregate size and zeta potential of nanoAg with different sizes (10 and 75 nm) and coatings (PVP and citrate) were measured in cell culture media. Results indicated that both PVP-coated nanoAg were less electronegative than their citrate-coated counterparts over all exposure times, but only the PVP-coated 10 nm particles retained their initial electronegativity over all exposure times. In addition, only the PVP-coated particles retained their initial sizes throughout the 3 h measurement. PVP-coated 10 nm nanoAg selectively altered the permeability of RBEC4 monolayers within a 15 min exposure, although high resolution microscopy indicated that all coated nanoAg distributed throughout the cell’s cytoplasm within the 3 h exposure. Reporter genes for AP-1 and NRF2/ARE, transfected into RBEC4, were selectively stimulated by the PVP-coated 10 nm nanoAg. Global gene arrays indicated that only PVP-coated nanoAg significantly altered gene expressions in the RBEC4, and those altered by 10 nm PVP-coated nanoAg were qualitatively similar but quantitatively much higher than those of its 75 nm counterpart. IPA and DAVID analyses indicated that the altered pathways affected by both PVP-coated nanoAg were primarily associated with a NRF2-mediated oxidative stress response, endocytosis, and bioenergetics. Together, these data suggest that the physicochemical features of surface coating aggregate size and surface charge contribute to capped nanoAg’s permeability and oxidative stress responses in RBEC4

Translocation and potential neurological effects of fine and ultrafine particles a critical update

Abstract Particulate air pollution has been associated with respiratory and cardiovascular disease. Evidence for cardiovascular and neurodegenerative effects of ambient particles was reviewed as part of a workshop. The purpose of this critical update is to summarize the evidence presented for the mechanisms involved in the translocation of particles from the lung to other organs and to highlight the potential of particles to cause neurodegenerative effects. Fine and ultrafine particles, after deposition on the surfactant film at the air-liquid interface, are displaced by surface forces exerted on them by surfactant film and may then interact with primary target cells upon this displacement. Ultrafine and fine particles can then penetrate through the different tissue compartments of the lungs and eventually reach the capillaries and circulating cells or constituents, e.g. erythrocytes. These particles are then translocated by the circulation to other organs including the liver, the spleen, the kidneys, the heart and the brain, where they may be deposited. It remains to be shown by which mechanisms ultrafine particles penetrate through pulmonary tissue and enter capillaries. In addition to translocation of ultrafine particles through the tissue, fine and coarse particles may be phagocytized by macrophages and dendritic cells which may carry the particles to lymph nodes in the lung or to those closely associated with the lungs. There is the potential for neurodegenerative consequence of particle entry to the brain. Histological evidence of neurodegeneration has been reported in both canine and human brains exposed to high ambient PM levels, suggesting the potential for neurotoxic consequences of PM-CNS entry. PM mediated damage may be caused by the oxidative stress pathway. Thus, oxidative stress due to nutrition, age, genetics among others may increase the susceptibility for neurodegenerative diseases. The relationship between PM exposure and CNS degeneration can also be detected under controlled experimental conditions. Transgenic mice (Apo E -/-), known to have high base line levels of oxidative stress, were exposed by inhalation to well characterized, concentrated ambient air pollution. Morphometric analysis of the CNS indicated unequivocally that the brain is a critical target for PM exposure and implicated oxidative stress as a predisposing factor that links PM exposure and susceptibility to neurodegeneration. Together, these data present evidence for potential translocation of ambient particles on organs distant from the lung and the neurodegenerative consequences of exposure to air pollutants.</p

The Physicochemistry of Capped Nanosilver Predicts Its Biological Activity in Rat Brain Endothelial Cells (RBEC4)

The “capping” or coating of nanosilver (nanoAg) extends its potency by limiting its oxidation and aggregation and stabilizing its size and shape. The ability of such coated nanoAg to alter the permeability and activate oxidative stress pathways in rat brain endothelial cells (RBEC4) was examined in the present study. The aggregate size and zeta potential of nanoAg with different sizes (10 and 75 nm) and coatings (PVP and citrate) were measured in cell culture media. Results indicated that both PVP-coated nanoAg were less electronegative than their citrate-coated counterparts over all exposure times, but only the PVP-coated 10 nm particles retained their initial electronegativity over all exposure times. In addition, only the PVP-coated particles retained their initial sizes throughout the 3 h measurement. PVP-coated 10 nm nanoAg selectively altered the permeability of RBEC4 monolayers within a 15 min exposure, although high resolution microscopy indicated that all coated nanoAg distributed throughout the cell’s cytoplasm within the 3 h exposure. Reporter genes for AP-1 and NRF2/ARE, transfected into RBEC4, were selectively stimulated by the PVP-coated 10 nm nanoAg. Global gene arrays indicated that only PVP-coated nanoAg significantly altered gene expressions in the RBEC4, and those altered by 10 nm PVP-coated nanoAg were qualitatively similar but quantitatively much higher than those of its 75 nm counterpart. IPA and DAVID analyses indicated that the altered pathways affected by both PVP-coated nanoAg were primarily associated with a NRF2-mediated oxidative stress response, endocytosis, and bioenergetics. Together, these data suggest that the physicochemical features of surface coating aggregate size and surface charge contribute to capped nanoAg’s permeability and oxidative stress responses in RBEC4